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Ampicillin Is a Substrate of Organic Anion Transporters 3
Yu-Ting Liu1, Xue-Yan Gou2, Lu Gan1
1School of Pharmacy, Lanzhou University, Lanzhou, Gansu, China.
None:
Ampicillin (AMP) is an organic anion drug widely used in clinical setting as a β-lactam antibiotic. However, the specific transporter involved in mediating AMP transport remains unidentified. Thus, we investigated whether organic anion transporters1/3 (OAT1/3) mediate the renal transport of AMP in this study. Both rOAT1/OAT3 (Slc22a6/Slc22a8) double-knockout and wild-type (WT) rats were administered AMP via intraperitoneal injection simultaneously. Following the knockout, a significant increase in AMP plasma concentration and the area under the plasma concentration-time curve (AUC) was observed, accompanied by a marked reduction in cumulative urinary excretion. OAT1/3-overexpressing cell uptake experiments demonstrated that AMP is a substrate of OAT3, with a Michaelis-Menten constant (Km) of 138.6 μM and a maximum transport velocity (Vmax) of 80.43 pmol/mg protein/min. In conclusion, AMP was identified as a substrate of OAT3, rather than OAT1.
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